Abstract 1332: Antiretroviral agent inhibits proliferation and motility of BT-20 cells through inhibition of human endogenous retrovirus type K

Abstract

Abstract The purpose of the study was to establish the role of human endogenous retrovirus K (HERV-K) in cancer development and to explore the possibility of repurposing antiretroviral agents for cancer treatment. We screened different categories of antiretroviral agents and several breast cancer cell lines to study the ability of antiretroviral agents to inhibit cancer cell proliferation and to inhibit the natural expression of HERV-K in cancer cells. Cells were transduced with exogenous HERV-K genes or with HERV-K knockdown plasmids to investigate the relationship between cytotoxic effect of antiretroviral agents and HERV expression. We found that an integrase strand-transfer inhibitor, dolutegravir, inhibited HERV-K expression on both the RNA and protein levels in BT-20 cells. Transduction with both HERV-K env and pol genes rendered the cell line more resistant to dolutegravir. Knockdown of HERV-K with shRNA also increased resistance to dolutegravir compared to cells transduced with random double-stranded RNA. The cytotoxic effect of dolutegravir correlated with enhanced expression of E-cadherin and a reduction in cell motility. Interestingly, an HERV-K knockdown cell line also exhibited enhanced expression of E-cadherin and reduced motility. As a potential carcinogenic role of HERVs has raised interest in using antiretroviral agents as a new approach to treat cancer, we provide the first evidence that one antiretroviral agent actually inhibits the proliferation and motility of a cancer cell line through inhibiting an HERV. Citation Format: John Lin, Mason Farris, Lauren Robbins, Matthew Lee, Serratt Nong, Yingguang Liu. Antiretroviral agent inhibits proliferation and motility of BT-20 cells through inhibition of human endogenous retrovirus type K [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1332.